Pehere, A.D.Nguyen, S.Garlick, S.K.Wilson, D.W.Hudson, I.Sykes, M.J.Morton, J.D.Abell, A.D.2019-03-312019-03-312019Bioorganic and Medicinal Chemistry, 2019; 27(2):436-4410968-08961464-3391http://hdl.handle.net/2440/118429The 26S proteasome and calpain are linked to a number of important human diseases. Here, we report a series of analogues of the prototypical tripeptide aldehyde inhibitor MG132 that show a unique combination of high activity and selectivity for calpains over proteasome. Tripeptide aldehydes (1-3) with an aromatic P3 substituent show enhanced activity and selectivity against ovine calpain 2 relative to chymotrypsin-like activity of proteasome. Docking studies reveal the key contacts between inhibitors and calpain to confirm the importance of the S3 pocket with respect to selectivity between calpains 1 and 2 and the proteasome.en© 2018 Elsevier Ltd. All rights reserved.Calpain inhibitors; 26S proteasome inhibitors; peptidomimetics; medicinal chemistryJournal article003010609510.1016/j.bmc.2018.12.0220004560820000192-s2.0-85058715666453745Wilson, D.W. [0000-0002-5073-1405]Abell, A.D. [0000-0002-0604-2629]